OBJECTIVE: Statins reduce inflammation and risk of myocardial infarction (MI). Because the myeloid IgA Fc receptor encoded by FCAR mediates inflammation, we hypothesized that the FCAR Asp92Asn polymorphism is associated with risk of MI and that this risk would be modified by pravastatin. METHODS AND RESULTS: In the placebo arm of the Cholesterol and Recurrent Events (CARE) study, male carriers of the 92Asn allele had an adjusted hazard ratio for incident MI of 1.68 (95% CI 1.10 to 2.57); relative risk reduction by pravastatin was 69% in carriers and 12% in noncarriers (P(interaction)=0.007). In the placebo arm of the all-male West of Scotland Coronary Prevention Study (WOSCOPS), carriers had an adjusted odds ratio for incident coronary heart disease (CHD) of 1.46 (90% CI 1.05 to 2.03); for pravastatin compared with placebo treatment, the adjusted odds ratios were 0.55 (95% CI 0.32 to 0.93) in carriers and 0.65 (95% CI 0.51 to 0.83) in noncarriers (P(interaction)=0.55). CONCLUSIONS: Carriers of 92Asn had increased risk of MI in CARE and increased odds of CHD in WOSCOPS. Pravastatin significantly reduced risk in carriers in both CARE and WOSCOPS. A genotype by treatment interaction was observed in CARE but not in WOSCOPS.
RCT Entities:
OBJECTIVE: Statins reduce inflammation and risk of myocardial infarction (MI). Because the myeloid IgA Fc receptor encoded by FCAR mediates inflammation, we hypothesized that the FCARAsp92Asn polymorphism is associated with risk of MI and that this risk would be modified by pravastatin. METHODS AND RESULTS: In the placebo arm of the Cholesterol and Recurrent Events (CARE) study, male carriers of the 92Asn allele had an adjusted hazard ratio for incident MI of 1.68 (95% CI 1.10 to 2.57); relative risk reduction by pravastatin was 69% in carriers and 12% in noncarriers (P(interaction)=0.007). In the placebo arm of the all-male West of Scotland Coronary Prevention Study (WOSCOPS), carriers had an adjusted odds ratio for incident coronary heart disease (CHD) of 1.46 (90% CI 1.05 to 2.03); for pravastatin compared with placebo treatment, the adjusted odds ratios were 0.55 (95% CI 0.32 to 0.93) in carriers and 0.65 (95% CI 0.51 to 0.83) in noncarriers (P(interaction)=0.55). CONCLUSIONS: Carriers of 92Asn had increased risk of MI in CARE and increased odds of CHD in WOSCOPS. Pravastatin significantly reduced risk in carriers in both CARE and WOSCOPS. A genotype by treatment interaction was observed in CARE but not in WOSCOPS.
Authors: Irene D Bezemer; Andre R Arellano; Carmen H Tong; Charles M Rowland; Helen A Ireland; Kenneth A Bauer; Joseph Catanese; Pieter H Reitsma; Carine J M Doggen; James J Devlin; Frits R Rosendaal; Lance A Bare Journal: Haematologica Date: 2009-03-13 Impact factor: 9.941
Authors: Kun Qian; Fenglong Xie; Andrew W Gibson; Jeffrey C Edberg; Robert P Kimberly; Jianming Wu Journal: J Leukoc Biol Date: 2008-09-10 Impact factor: 4.962
Authors: Alanna C Morrison; Lance A Bare; May M Luke; James S Pankow; Thomas H Mosley; James J Devlin; James T Willerson; Eric Boerwinkle Journal: Cerebrovasc Dis Date: 2008-09-18 Impact factor: 2.762
Authors: Jeroen B van der Net; Daniëlla M Oosterveer; Jorie Versmissen; Joep C Defesche; Mojgan Yazdanpanah; Bradley E Aouizerat; Ewout W Steyerberg; Mary J Malloy; Clive R Pullinger; John J P Kastelein; John P Kane; Eric J G Sijbrands Journal: Eur Heart J Date: 2008-07-03 Impact factor: 29.983
Authors: Dov Shiffman; Ellen S O'Meara; Lance A Bare; Charles M Rowland; Judy Z Louie; Andre R Arellano; Thomas Lumley; Kenneth Rice; Olga Iakoubova; May M Luke; Bradford A Young; Mary J Malloy; John P Kane; Stephen G Ellis; Russell P Tracy; James J Devlin; Bruce M Psaty Journal: Arterioscler Thromb Vasc Biol Date: 2007-11-01 Impact factor: 8.311
Authors: May M Luke; Ellen S O'Meara; Charles M Rowland; Dov Shiffman; Lance A Bare; Andre R Arellano; W T Longstreth; Thomas Lumley; Kenneth Rice; Russell P Tracy; James J Devlin; Bruce M Psaty Journal: Stroke Date: 2008-11-20 Impact factor: 7.914
Authors: J L Mega; N O Stitziel; S Kathiresan; M S Sabatine; J G Smith; D I Chasman; M Caulfield; J J Devlin; F Nordio; C Hyde; C P Cannon; F Sacks; N Poulter; P Sever; P M Ridker; E Braunwald; O Melander Journal: Lancet Date: 2015-03-04 Impact factor: 79.321